Characterization of functional and phenotypic changes in anti-Gag vaccine-induced T cell responses and their role in protection after HIV-1 infection
Characterization of functional and phenotypic changes in anti-Gag vaccine-induced T cell responses and their role in protection after HIV-1 infection
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DOI：
10.1073/pnas.0408773102
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发表时间：
2005-03-22
影响因子：
11.1
通讯作者：
Ferrari, G
中科院分区：
文献类型：
--
作者：
Betts, MR;Exley, B;Ferrari, G
世界范围内的HIV-1疫苗工作的指导原则是HIV特异性T细胞反应可以提供保护免受感染或延迟明显的疾病。然而，没有明确的相关性T细胞介导的免疫保护已被确定。在这里，我们研究了HLA-B27（+）HIV血清阴性疫苗接种者持续的HIV特异性疫苗诱导的抗Gag CD 4（+）和CD 8（+）T细胞应答。尽管这些应答表现出预测与感染保护相关的特征（多功能性、适当的记忆表型和与长期非进展相关的表位靶向），但受试者感染了HIV。HIV感染后，疫苗诱导的CD 8（+）T细胞扩增，但CD 4（+）和CD 8（+）T细胞应答均获得慢性HIV感染的功能和表型特征。病毒很快就逃脱了疫苗诱导的T细胞反应，受试者的进展速度比表达HLA-B27等位基因的人预期的要快。这些数据表明，通过疫苗引起的HIV特异性T细胞应答来控制HIV可能是困难的，即使T细胞应答具有预测提供最佳保护的那些特征。
Worldwide HIV-1 vaccine efforts are guided by the principle that HIV-specific T cell responses may provide protection from infection or delay overt disease. However, no clear correlates of T cell-mediated immune protection have been identified. Here, we examine in a HLA-B27(+) HIV seronegative vaccinee persistent HIVspecific vaccine-induced anti-Gag CD4(+) and CD8(+) T cell responses. Although these responses exhibited those characteristics (multi-functionality, appropriate memory phenotype, and targeting of epitopes associated with long-term nonprogression) predicted to correlate with protection from infection, the subject became HIV infected. After HIV infection, the vaccine-induced CD8(+) T cells expanded, but both CD4(+) and CD8(+) T cell responses acquired the functional and phenotypic patterns characteristic of chronic HIV infection. The virus quickly escaped the vaccine-induced T cell response, and the subject progressed more rapidly than expected for someone expressing the HLA-B27 allele. These data suggest that control of HIV by vaccine-elicited HIV-specific T cell responses may be difficult, even when the T cell response has those characteristics predicted to provide optimal protection.